Transfusion medicine
Transfusion transmitted disease
Bacteria-general


Topic Completed: 6 July 2020

Minor changes: 16 July 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Bacterial contamination[TIAB] transfusions[TIAB] full text[SB]

Jessica Corean, M.D.
Ryan A. Metcalf, M.D.
Page views in 2019: 12
Page views in 2020 to date: 102
Cite this page: Corean J, Metcalf RA. Bacteria-general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/transfusionmedbacterialcontamination.html. Accessed October 29th, 2020.
Definition / general
  • Transfusion transmitted bacterial infections (TTBI) present with fever, chills and hypotension immediately or up to 24 hours after a transfusion
  • Platelets are by far the most commonly bacterially contaminated blood component due to room temperature storage and TTBI is one of the leading causes of death due to transfusion each year
  • Bacterial risk control strategies for platelets include donor testing for bacteria and pathogen reduction technology (PRT)
Essential features
Terminology
  • Transfusion transmitted bacterial infection (TTBI)
  • Intravenous drug use (IVDU)
  • Transfusion related acute lung injury (TRALI)
  • Whole blood derived (WBD)
  • Disseminated intravascular coagulation (DIC)
  • Pathogen reduction technology (PRT)
  • Large volume delayed sampling (LVDS)
Pathophysiology
  • Bacteria on donor skin or asymptomatic bacteremia that transfers to the collected blood component
  • Bacteria proliferate at a rate that is dependent on lag time, doubling time and growth medium (the heterogeneous platelet component)
  • Most common bacterial pathogens detected in blood components
    • Staphylococcus epidermidis and Staphylococcus aureus
    • Gram negative bacteria, such as Klebsiella species
    • Anaerobic bacteria, such as Clostridium perfringens and Propionibacterium / Cutibacterium species (this latter category of organisms may have limited pathogenic potential)
  • Bacterial risk control strategies (such as donor arm disinfection, diversion, testing and careful visual inspection of product prior to release) fail (Vox Sang 2014;106:23)
  • Transfusion of bacteria above a certain threshold of harm (e.g. 103 - 105 colony forming units/ml) causes systemic inflammatory response in patient: fever, chills, hypotension (Clin Infect Dis 2008;46:1214, Transfusion 2017;57:2174)
  • Platelet components most commonly implicated due to room temperature storage
  • Rarely, bacterially contaminated red blood cell components have been reported to cause septic transfusion reactions
Clinical features
  • TTBI rate likely underreported due to passive reporting of suspected transfusion reactions (Blood 2016;127:496)
  • Surveillance data demonstrate nearly all septic transfusion reactions are associated with platelets issued on the last 2 days of shelf life (Transfusion 2020;60:220)
Transmission
  • Bacteria are transferred from donor into collected blood component(s) and bacterial risk control strategies fail to result in interdiction of component(s)
  • Contaminated blood component is transfused into the blood stream of a transfusion recipient
Symptoms
Screening
  • Note that pathogen reduction technology does not require bacterial testing (screening)
  • Permissible risk control strategies using FDA approved methods are outlined below with some useful naming codes in parentheses:
    • Apheresis platelets or prestorage pools of whole blood derived platelets
      • Single step methods:
        • Primary culture no sooner than 24 hours, 3 day shelf life (24C-3)
        • Large volume delayed sampling at 36 hours postcollection, 5 day shelf life (36C-5)
        • Large volume delayed sampling at 48 hours, 7 day shelf life (48C-7)
        • Pathogen reduction technology, 5 day shelf life (PRT)
      • 2 step methods:
        • Primary culture no sooner than 24 hours with secondary culture performed no sooner than day 3, 5 day shelf life (24C-D3C-5)
        • Primary culture no sooner than 24 hours with secondary culture no sooner than day 4, 7 day shelf life (24C-D4C-7)
        • Primary culture no sooner than 24 hours with rapid testing, 5 day shelf life (24C-R-5)
        • Primary culture no sooner than 24 hours with rapid testing, 7 day shelf life (24C-R-7)
        • Large volume delayed sampling no sooner than 36 hours with secondary culture no sooner than day 4, 7 day shelf life (36C-D4C-7)
        • Large volume delayed sampling no sooner than 36 hours with secondary rapid testing, 7 day shelf life (36C-R-7)
    • Single units and poststorage pools of whole blood derived platelets

List of permissible bacterial risk control testing policies for apheresis platelets and their characteristics
Policy code Primary culture Component
expiration
time
(hours)
Secondary test Availability
(hours)
Sample
time
(hours)
Hold
time
(hours)
Test
type
Sample
time
(hours)
Hold
time
(hours)
24C-3 24 12 72 N/A N/A N/A 36
36C-5 36 12 120 N/A N/A N/A 72
48C-7 48 12 168 N/A N/A N/A 108
24C-D3C-5 24 N/A 120 culture 72 * 72
24C-D4C-7 24 N/A 168 culture 96 12 120
36C-D4C-7 36 N/A 168 culture 96 12 108
24C-R-5 24 N/A 120 rapid 12 hours prior
to issue
N/A 84
24C-R-7 24 N/A 168 rapid 12 hours prior
to issue
N/A 132
36C-R-7 36 N/A 168 rapid 12 hours prior
to issue
N/A 120

*Time period not specifically defined in FDA guidance; a hold period is required in the guidance but not specified for this testing policy (Walker BS et al. The comparative safety of bacterial risk control strategies for platelet components: A simulation study. Transfusion. Accepted.)

  • False positive results are not uncommon
    • If bacterial testing is positive, recommend sampling the platelet bag for a confirmation culture
    • Organism should be identified and retrieval of any co-components is required
  • Donor should be notified if bacteria not a likely skin contaminant
  • Non-PRT strategies (i.e. those involving testing) have residual risk of contamination and septic transfusion reactions due to false negative results, which depends on strategy used and bacterial growth characteristics (Transfusion 2018;58:1647, Vox Sang 2012;103:1)
Blood donor screening
  • Questionnaire, specifically, to address illness within few days before / after donation
  • Vitals within normal limits
  • Antecubital skin examination: free of lesions and evidence of intravenous drug use (Fung: Technical Manual, 19th Edition, 2017)
Blood donor testing
  • No specific bacterial testing of donors is performed directly, only on collected components
  • Bacterial contamination is mitigated by improved donor skin disinfection and diversion of first 10 - 40 mL of donor blood
Donor deferral
  • Medical director dependent, likely indefinite or permanent deferral
Laboratory
  • When a septic transfusion reaction is suspected, bacterial culture of remaining transfused component and patient blood culture with same organism identified
  • Gram stain of the residual transfusion component may be positive for bacteria
  • Direct antiglobulin test (DAT) and visual inspection for hemolysis are usually negative
  • Clerical check and repeat of patient ABO expected to be correct (Fung: Technical Manual, 19th Edition, 2017)
Case reports
Treatment
  • Stop the transfusion immediately
  • Broad spectrum antibiotics until bacterial sensitivity / specificity known, then optimize coverage
  • Supportive care
  • Quarantine any co-components still in inventory as quickly as possible (Fung: Technical Manual, 19th Edition, 2017)
Sample assessment & plan
  • Assessment: Patient X is a 50 year old male with acute myeloid leukemia undergoing hematopoietic stem cell transplant. He received a unit of apheresis platelets for bleeding prophylaxis (platelet count 5,000/uL). Within 1 hour of starting the transfusion, he developed tachycardia, hypotension and chills. The transfusion was stopped. A suspected transfusion reaction investigation was initiated with return of the component and associated tubing and a new blood sample to the Transfusion Service. Clerical check was correct. Visual hemolysis and DAT were negative. ABO was correct. Patient blood culture and residual platelet component culture were positive for Staphylococcus aureus.
  • Plan: Supportive care and extended spectrum antibiotic coverage followed by more specific coverage when organism is identified and sensitivities performed. Quarantine any co-components. The patient may receive future transfusions as clinically indicated.
Differential diagnosis
Board review style question #1
A 65 year old man with a history of acute lymphoblastic leukemia is undergoing induction and has required multiple transfusions for anemia and thrombocytopenia. During a platelet transfusion, he develops fever, chills and hypotension. The transfusion is stopped and the product is returned to the Transfusion Service. Chest Xray shows no pulmonary edema or infiltrates. The Transfusion Service reports no hemolysis and the DAT is negative. What is the next most important step?

  1. The patient should be given an antihistamine
  2. The patient should be transferred to the ICU for close monitoring
  3. The patient should receive an antipyretic medication
  4. The patient's blood and the residual product should be cultured and the patient should be treated empirically with antibiotics
  5. The product and any other products created from the same donation should be thrown away
Board review answer #1
D. The patient and the residual product should be cultured for aerobic and anaerobic bacteria. Additionally, a Gram stain should be performed to immediately provide clinicians a preliminary identification but are variably negative. If the cultures are positive, the organism should be the same. Additional testing, such as pulsed field gel electrophoresis of DNA macrorestriction, can lend information as to the similarities of the bacterial isolates. Since culture is a time intensive process, if there is clinical concern for a TTBI, the patient should be empirically treated with broad spectrum antibacterial coverage until identification with antibiotic sensitivities are available. While additional donor products should be identified and isolated, the products should be cultured, not thrown away. The ICU is likely necessary in a septic patient but further workup is still necessary for a diagnosis. The patient does not have symptoms solely suggestive of an allergic reaction, which would include urticarial, angioedema, bronchospasm, etc. An antipyrectic medication may be appropriate but the hypotension is concerning for a more serious transfusion reaction than a febrile, nonhemolytic reaction.

Comment Here

Reference: Bacterial contamination of blood components
Board review style question #2
A donor presents to donate an apheresis platelet. The donor history questionnaire, vitals and hemoglobin / hematocrit are acceptable. The donor donates without incident. Viral testing returns negative. The product is cultured at 24 hours. According to the September 2019 FDA guidance, what is one permissible next step?

  1. After the appropriate amount of hold time (12 hours), the product is ready for transfusion with a 7 day shelf life
  2. After the appropriate hold period (12 hours), the product is ready for transfusion with a 4 day shelf life
  3. Rapid testing may be used according to the manufacturer's package insert with up to a 7 day shelf life of the platelet product
  4. Secondary culture cannot be used to extend shelf life
Board review answer #2
C. Rapid testing may be used according to the manufacturer's package insert with up to a 7 day shelf life of the platelet product. The product is an apheresis platelet with a primary culture performed at 24 hours, which without a subsequent secondary test, has a shelf life of 3 days. A secondary test may be used to extend the shelf life. These may include rapid testing or secondary culture no sooner than day 4 for up to a 7 day shelf life. These strategies are based on the September 2019 FDA Guidance, which has several permissible strategies that are outlined above in this chapter.

Comment Here

Reference: Bacterial contamination of blood components
Back to top
Image 01 Image 02